Activation of TIM1 induces colon cancer cell apoptosis via modulating Fas ligand expression
Hao Wang1, Xueyan Zhang1, Wenjing Sun2
1Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150086, China.
Abstract:
The pathogenesis of colon cancer is unclear. It is proposed that TIM1 has an association with human cancer. The present study aims to investigate the role of TIM1 activation in the inhibition of human colon cancer cells. In this study, human colon cancer cell line, HT29 and T84 cells were cultured. The expression of TIM1 was assessed by real time RT-PCR and Western blotting. The TIM1 on the cancer cells was activated in the culture by adding recombinant TIM4. The chromatin structure at the FasL promoter locus was assessed by chromatin immunoprecipitation. The apoptosis of the cancer cells was assessed by flow cytometry. The results showed that human colon cancer cell lines, HT29 cells and T84 cells, expressed TIM1. Activation of TIM1 by exposing the cells to TIM4 significantly increased the frequency of apoptotic colon cancer cells. The expression of FasL was increased in the cancer cells after treating by TIM4. Blocking Fas or FasL abolished the exposure to TIM4-induced T84 cell apoptosis. In conclusion, HT29 cells and T84 cells express TIM1; activation TIM1 can induce the cancer cell apoptosis. TIM1 may be a novel therapeutic target of colon cancer.
Insights
Activation of TIM1 in colon cancer cells induces apoptosis, suggesting TIM1 as a potential therapeutic target for colon cancer treatment. This study explored TIM1
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- The precise mechanisms driving colon cancer development remain incompletely understood.
- Tumor-induced myeloidexpressed gene 1 (TIM1) has been implicated in various human cancers.
- Investigating TIM1's role offers potential for novel therapeutic strategies in colon cancer.
Purpose of the Study:
- To elucidate the function of TIM1 activation in suppressing human colon cancer cell proliferation.
- To determine if TIM1 can serve as a therapeutic target for colon cancer.
Main Methods:
- Cultured human colon cancer cell lines (HT29 and T84).
- Assessed TIM1 expression using real-time RT-PCR and Western blotting.
- Activated TIM1 with recombinant TIM4, analyzed apoptosis via flow cytometry, and examined FasL promoter activity using chromatin immunoprecipitation.
Main Results:
- Both HT29 and T84 colon cancer cells express TIM1.
- TIM1 activation by TIM4 significantly enhanced colon cancer cell apoptosis.
- TIM4 treatment increased FasL expression, and blocking Fas/FasL pathways abrogated TIM4-induced apoptosis.
Conclusions:
- TIM1 is expressed in human colon cancer cell lines HT29 and T84.
- TIM1 activation effectively induces apoptosis in colon cancer cells.
- TIM1 represents a promising novel therapeutic target for colon cancer intervention.
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